The HERG (human ether-a-go-go-related) gene encodes a membrane protein that functions as a K+ -channel. There is intense interest in the HERG protein because interactions between drugs and the HERG channel protein have become a major impediment in the development of new and safe pharmaceuticals. Interactions of drugs with the HERG channel alter the repolarization of the hearts' electrical system, causing tachycardia and occasionally heart failure. This has led to the removal of at least one drug from the market, and caused many others to fail in clinical trials. There is an increasing demand for methodologies that will allow prediction and identification of lead compounds with potential HERG channel activity early in the drug discovery process. The specific aims of this proposal are to develop multiple ligand binding assays and a functional assay for the HERG channel, as expressed in CHO cells. Once developed, approximately 20 known HERG inhibiting drugs will be screened for dose response in all assays developed and the data collected and assembled in a database. This database will then be used as the basis for a Phase 2 study that greatly expands the chemicals tested, to identify key molecular and chemical descriptors that are predictive of drug and protein interactions with the channel.